The human brain processes sensory input flexibly to extract the most useful information and generate the most advantageous response given current behavioral strategies and goals. Computational flexibility of this type is often referred to as executive control, particularly when it involves the brain selecting to implement one cognitive process over another in order to determine the best course of action within a given context. We have a limited understanding of how executive control, as such, is mediated by physiological events in cortical neurons. To increase our knowledge of the cellular basis of executive control, I propose to simultaneously record the electrical activity of ensembles of 20-30 individually isolated neurons in prefrontal cortex (area 46) and in posterior parietal cortex (area 7a) of monkeys as they perform a task requiring them to exert executive control over spatial cognition. Specifically, monkeys will assign visual stimuli to alternative spatial categories according to a variable grouping criterion (rule) that we instruct and change on a trial-by-trial basis. In this task, we present a line that serves as a category boundary, and define spatial categories as groups of spatial positions that bear the same spatial relationship to the line - such that, for example, all points to the left of the line comprise one category, and all points to the right another. By shifting and rotating the boundary, we require the brain to flexibly reassign a fixed set of spatial positions to alternative spatial categories in a rule- dependent manner, and this requires the brain to exert executive control over spatial categorization as a cognitive and physiological process. Our objective is to discover how executive control over spatial categorization is implemented at a cellular level, by measuring rule-dependent changes in distributed neural representations of the spatial category to which the brain has assigned a stimulus under a given rule. We will test the hypothesis that rule-dependent changes in category representation will emerge first and be strongest in prefrontal cortex. This will support our hypothesis that prefrontal cortex sits above parietal cortex in a hierarchy of areas mediating executive control over cognitive processing in distributed cortical systems, and provide some of the first detail about the neural mechanisms by which this control is implemented at a cellular level. PUBLIC HEALTH RELEVANCE: The research described in this proposal investigates the neural mechanisms of executive control in prefrontal cortical networks of the nonhuman primate brain. Executive control refers to the capacity of the brain to selectively implement alternative cognitive processes on the basis of behavioral rules, goals or strategies. To understand how executive control is implemented by cortical neurons, we will record the electrical activity of groups of neurons in the prefrontal and posterior parietal cortex of monkeys as they perform a task in which rules govern spatial cognitive processing. Prefrontal and parietal cortexes are anatomically connected and jointly support spatial cognitive function. By discovering how rules modulate patterns of electrical activity associated with cognitive processing in this cortical network, we will be able to discover how executive control is implemented at a cellular level, and further determine whether prefrontal cortex plays a predominant role in mediating executive control. This in turn will help us understand the neural processes that may be disrupted to produce deficits in executive function in human diseases, such as prefrontal stroke, or schizophrenia.